Avelumab, New Therapy for Metastatic Merkel Cell and Urothelial Carcinomas

Immunotherapy is a type of treatment that uses substances to stimulate or suppress the immune system to help the body fight cancer. Scientists discovered that certain proteins found on T cells and cancers keep immune responses in check and prevent them from killing cancer cells. Monoclonal antibodies block these “checkpoint” proteins and, when blocked, the immune system can be released and is better able to kill cancer cells. Avelumab (Bavencio®) is a human, monoclonal antibody that targets the PD-L1 checkpoint protein.

Through a Cooperative Research and Development Agreement (CRADA) with EMD Serono, the National Cancer Institute (NCI) played an instrumental role in developing and expediting regulatory approval of EMD Serono’s checkpoint inhibitor avelumab. Through this CRADA NCI performed early, preclinical studies that evaluated its efficacy and produced promising results, and published data showing avelumab’s ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). NCI conducted several critical studies that led to FDA approval for patients with urothelial carcinoma (bladder cancer) and Merkel cell carcinoma (MCC).

Once these studies demonstrated positive results, the clinical trial was quickly opened up to accommodate multiple patient groups; NCI participated in many of these expansion cohorts. To date, over 1,700 patients have been enrolled in this single study and received treatment with investigational avelumab. From the point when EMD Serono and NCI amended their existing CRADA in 2013 to include the study of avelumab, they received FDA approval in 2017 for two indications—a remarkably fast developmental and regulatory approval timeline of four years.

By November 2016, the FDA granted avelumab a Biologics License Application (BLA) Priority review for Metastatic MCC, an FDA license that accelerates approval. In March 2017, the FDA approved avelumab for metastatic MCC, a rare skin cancer for which there was no previously FDA-approved treatment. In September 2017, the European Commission and Switzerland also granted approval. These approvals address a significant, unmet medical need. MCC is rarer than some more well-known skin cancers; it is very aggressive, and the proportion of people who die from it is much higher than those with melanoma.

In February 2017, FDA granted a BLA for avelumab for urothelial carcinoma. Three months later, the FDA approved avelumab for urothelial carcinoma that has been previously treated, locally advanced, or metastasized. Bladder cancer makes up approximately 90 percent of urothelial carcinomas, and is the sixth most common cancer in the U.S. When the disease has metastasized, the five-year survival rate is approximately five percent. Despite treatment advances, the prognosis for these patients remains poor. Avelumab’s approval provides an important treatment option that will hopefully improve outcomes for these patients.